Pyrazolopyridazine alpha-2-delta-1 ligands for the treatment of neuropathic pain

Autor:	Mark Patrick Healy, Karamjit S. Jandu, Kim L. Matthews, James E. Rowedder, Clement Douault, Wenjing Meng, Andrew Billinton, Jason Witherington, Anne Hersey, Rino A. Bit, Nick M. Clayton, James Myatt, Gianpaolo Bravi, Christopher N. Johnson, Jason D. Brown, Livermore David
Rok vydání:	2010
Předmět:	Calcium Channels L-Type Stereochemistry Pyridines Clinical Biochemistry Analgesic Pharmaceutical Science Ligands Biochemistry Structure-Activity Relationship In vivo Drug Discovery Animals ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Biology Analgesics Chemistry Ligand Organic Chemistry Calcium Channel Blockers In vitro Rats Pyridazines Neuropathic pain Molecular Medicine Neuralgia Pyrazoles Alpha-2 adrenergic receptor Efflux Calcium Channels Selectivity
Zdroj:	Bioorganicmedicinal chemistry letters. 20(15)
ISSN:	1464-3405
Popis:	Optimization of the novel alpha-2-delta-1 ligand 4 provided compounds 37 and 38 which have improved DMPK profiles, good in vivo analgesic activity and in vitro selectivity over alpha-2-delta-2. An in-house P-gp prediction programme and the MetaSite software package were used to help solve the specific problems of high P-gp efflux and high in vivo clearance.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3458a53f33f9346e250b627e4ae61f95 https://pubmed.ncbi.nlm.nih.gov/20566291 Zobrazit plný text záznamu Full Text from ScienceDirect